ArticleNature medicine2025
Genetic subtyping of obesity reveals biological insights into the uncoupling of adiposity from its cardiometabolic comorbidities.
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Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19citing papers in PubMed
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Who cites it
19 citing papers in PubMed.
- Extreme Obesity (BMI ≥ 60 kg/mObesity (Silver Spring, Md.) · 2026Article
- Type 2 diabetes prevention across the life course.Nature medicine · 2026Review
- The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026Review
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- Hepatic FXR deficiency exacerbates dyslipidemia by disrupting the gut-liver axis via bile acid disorder and gut microbiota dysbiosis.Journal of translational medicine · 2026Article
- From GWAS Signals to Molecular Mechanisms: Explainable AI for Causal Gene Prioritization and Biomolecular Target Interpretation.Biomolecules · 2026Review
- Metabolic and Glycemic Effects of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta-Analysis of Randomised Clinical Trials.Endocrinology, diabetes & metabolism · 2026Article
- Hyperinsulinaemia as a cause of obesity and cardiometabolic diseases.Nature reviews. Endocrinology · 2026Review
- Article
- Data-Driven Decision Support in Obesity Management Commission: enabling more equitable and personalized obesity care.Nature medicine · 2026Article
- A data-driven risk stratification framework for clinical obesity.Nature medicine · 2026Article
- Mediterranean Diet Can Reduce Fat Accumulation and Obesity Progression Through Action of Plant Bioactive Molecules.International journal of molecular sciences · 2026Review
- The genetics of obesity: aetiology, prevention and therapy.Nature metabolism · 2026Review
- Data-driven glycolipid network phenotypes reveal a graded risk spectrum for cardiometabolic multimorbidity: a prospective study in middle-aged and older Chinese adults.Lipids in health and disease · 2026Article
- The polygenic, omnigenic and stratagenic models of complex disease risk.Nature genetics · 2026Review
- Diagnostic and therapeutic innovations in myocardial infarction: a focus on mitochondrial dysfunction.Frontiers in cardiovascular medicine · 2026Review
- Central adiposity and sex influence lipid and glucose indices in Mexican adults: implications for metabolic risk assessment.Frontiers in nutrition · 2026Article
- Obesity care in Chinese adults: from evidence to clinical practice.Precision clinical medicine · 2025Review
Corrections and comments
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Authors and funding
19 authors.
Nathalie Chami *The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Zhe Wang *The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-8046-4969
Victor SvenstrupThe Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0009-0002-5725-8865
Virginia Diez ObreroThe Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Daiane HemerichThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Yi HuangThe Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5734-650X
Hesam DashtiThe Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Eleonora ManittaThe Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Michael H PreussThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-5266-8465
Kari E NorthDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-8903-0366
Louise Aas HolmThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-5439-5429
Cilius E FonvigThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-5031-0125
Jens-Christian HolmThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-4653-342X
Torben HansenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-8748-3831
Camilla ScheeleThe Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6055-9709
Alexander RauchDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark.
Roelof A J SmitThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Melina ClaussnitzerThe Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ruth J F LoosThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ruth.loos@sund.ku.dk.ORCID http://orcid.org/0000-0002-8532-5087
Funding
Conduits: Mount Sinai Health System Translational Science HubUL1TR004419 · NCATS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Rosalind J Wright · 2022 to 2026
$46.4MROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Elizabeth Austen Lawson, Takara Leah Stanley · 1994 to 2026
$31.6MTHE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - COORDINATING CENTER - TASK AREA B.2 AND B.375N92022D00001 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COUPER, DAVID · 2022 to 2025
$13.7MCell Interactions in the Inflamed Intestinal MucosaR01DK075787 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI JOEL N HIRSCHHORN · 2007 to 2026
$13.1MPolygenic Risk Scores for Diverse Populations - Bridging Research and Clinical CareR01HL151152 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Christy Leigh Avery, Jennifer Below · 2020 to 2026
$12.3MBridging the gap between type 2 diabetes GWAS and therapeutic targetsUM1DK126185 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CLAUSSNITZER, MELINA C, GLOYN, ANNA LOUISE · 2020 to 2024
$9.5MA Multi-Ancestry Study of Gene-Lifestyle Interactions and Multi-Omics in Cardiometabolic TraitsR01HL156991 · NHLBI · WASHINGTON UNIVERSITY · PI RAO, DABEERU C · 2021 to 2024
$8.8MPAGE III: Population Architecture using Genomics and EpidemiologyR01HG010297 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI GIGNOUX, CHRISTOPHER R, MATISE, TARA C. · 2019 to 2022
$6.5MHispanic Latino Lipid ConsortiumR01HL142302 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jennifer Below, JOSEPH MCCORMICK · 2018 to 2026
$5.8MDevelopment of Polygenic Risk Scores for Diabetes and Complications across the Life-Span in Populations of Multiple AncestriesU01HG011723 · NHGRI · BROAD INSTITUTE, INC. · PI Alisa Knodle Manning, Josep Maria Mercader · 2021 to 2026
$5.7MCardiorenal Genomics for Risk Prediction in African Descent PopulationsR35HL155466 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Marguerite R Irvin · 2021 to 2026
$5.1MTHE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00003 · NHLBI · UNIVERSITY OF MINNESOTA · PI LUTSEY, PAMELA L. · 2022 to 2025
$5.1MNCATS NIH HHS UL1 TR004419NHGRI NIH HHS R01 HG010297NHGRI NIH HHS U01 HG007417NHGRI NIH HHS U01 HG011723NHLBI NIH HHS 75N92022D00001NHLBI NIH HHS 75N92022D00002NHLBI NIH HHS 75N92022D00003NHLBI NIH HHS 75N92022D00004NHLBI NIH HHS 75N92022D00005NHLBI NIH HHS R01 HL142302NHLBI NIH HHS R01 HL151152NHLBI NIH HHS R01 HL156991NHLBI NIH HHS R01 HL158884NHLBI NIH HHS R01 HL163262NHLBI NIH HHS R35 HL155466NIDDK NIH HHS P30 DK040561NIDDK NIH HHS R01 DK075787NIDDK NIH HHS R01 DK102173NIDDK NIH HHS R01 DK107786NIDDK NIH HHS R01 DK110113NIDDK NIH HHS R01 DK122503NIDDK NIH HHS R01 DK123019NIDDK NIH HHS R01 DK139598NIDDK NIH HHS UM1 DK126185NIH HHS S10 OD026880NIH HHS S10 OD030463Novo Nordisk Fonden (Novo Nordisk Foundation) NNF22SA0079901U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK110113
Abstract
Obesity is a heterogeneous condition not adequately captured by a single adiposity trait. We conducted a multi-trait genome-wide association analysis using individual-level data from 452,768 UK Biobank participants to study obesity in relation to cardiometabolic health. We defined continuous 'uncoupling phenotypes', ranging from high adiposity with healthy cardiometabolic profiles to low adiposity with unhealthy ones. We identified 266 variants across 205 genomic loci where adiposity-increasing alleles were simultaneously associated with lower cardiometabolic risk. A genetic risk score (GRS
Indexed as
AdiposityCardiovascular DiseasesObesityAdultAgedComorbidityFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedPhenotypePolymorphism, Single NucleotideRisk FactorsUnited Kingdom
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